Support for the "Bad Old Blood" rather than "Good Young Blood" View of what is Taking Place in Heterochronic Parabiosis

Join the circulatory systems of two mice, one young and one old, a procedure known as heterochronic parabiosis, and the young one suffers some of the impact of aging while the old one loses some of that same impact. Regenerative capacity and stem cell activity are affected, for example. Researchers continue to search for factors in the blood that might explain this, but this work is still in its comparatively early stages. The question of the degree to which the mechanisms involve beneficial factors in young blood or harmful factors in old blood remains to be settled, with a range of interesting evidence on both sides. The "bad old blood" view seems to have the more compelling demonstration so far, I feel. If this is the case, benefits in the old mice are realized because the harmful factors in old blood are diluted by young blood, not because the young blood is providing beneficial signals.

Aging is a gradual biological process characterized by a decrease in cell and organism functions. Gingival wound healing is one of the impaired processes found in old rats. Here, we studied the in vivo wound healing process using a gingival repair rat model and an in vitro model using human gingival fibroblasts for cellular responses associated to wound healing. To do that, we evaluated cell proliferation of both epithelial and connective tissue cells in gingival wounds and found decreased of Ki67 nuclear staining in old rats when compared to their young counterparts.

We next evaluated cellular responses of primary gingival fibroblast obtained from young subjects in the presence of human blood serum of individuals of different ages. Eighteen to sixty five years old masculine donors were classified into 3 groups: "young" from 18 to 22 years old, "middle-aged" from 30 to 48 years old and "aged" over 50 years old. Cell proliferation, measured through immunofluorescence for Ki67 and flow cytometry for DNA content, was decreased when middle-aged and aged serum was added to gingival fibroblasts compared to young serum. Myofibroblastic differentiation, measured through alpha-smooth muscle actin (α-SMA), was stimulated with young but not middle-aged or aged serum both the protein levels and incorporation of α-SMA into actin stress fibers. High levels of PDGF, VEGF, IL-6R were detected in blood serum from young subjects when compared to middle-aged and aged donors. In addition, the pro-inflammatory cytokines MCP-1 and TNF were increased in the serum of aged donors.

In wounds in old rats there is an increased of staining for TNF compared to young rat wounds. Moreover, healthy gingiva (non injury) shows less staining compared to a wound site, suggesting a role in wound healing. Moreover, serum from middle-aged and aged donors was able to stimulate cellular senescence in young cells as determined by the expression of senescence associated beta-galactosidase and histone H2A.X phosphorylated at Ser139. Further, we detected an increased frequency of γ-H2A.X-positive cells in aged rat gingival tissues. The present study suggests that serum factors present in middle-aged and aged individuals may be responsible, at least in part, for the altered responses observed during wound healing in aging.

Link: https://doi.org/10.1371/journal.pone.0184189

Comments

If this turns out to be the case, that harmful factors in old blood are the culprit, then it should not be that hard to identify those factors and remove them from our blood with some kind of filter, right? The end therapy would then be some kind of dialysis.

Posted by: DarwiN at September 14th, 2017 2:25 PM

@DarwiN : I really hope so. I'm sick of the media spin making it out to be a bunch of Vampires sucking out the life-force of the young. If its a matter of "fixing the old", not only is it easier to get funding for more basic science, the young won't feel victimized.

Science isn't always pretty, and often it takes breaking societal norms to show effectiveness. After you get good results and a solution everyone wants on board the life-train.

Heart transplants are a great example.

Posted by: Mark Borbely at September 14th, 2017 3:45 PM

Is this evidence for the SENS RF view that there are 7 categories of damage, and evidence against the hallmarks of aging view of loss of protein organization?

Posted by: Jim at September 15th, 2017 12:18 AM

@Jim: I don't think it supports either side, beyond tangential support for the relevance of cellular senescence.

Posted by: Reason at September 15th, 2017 7:02 AM

@Jim it isn't a case of SENS vs Hallmarks. Loss of Proteostasis is part of both as they result in the accumulation of amyloids. The only difference here is how those damages are named basically. We need to stop thinking of this as a theory vs theory thing and focus on the much larger amount of common ground both of these have.

The Conboys are convinced the negative factors in aged blood are the problem and that there isn't a secret sauce in young blood, having reviewed the data I am inclined to agree with them. Dilution is a compelling explanation in my view.

Posted by: Steve Hill at September 15th, 2017 8:35 AM

Also, factorial signalling is more the Hallmark: Altered intercellular communication which encompasses "inflammaging" and would include pro-aging signalling factors like TGF-beta, CD38, TNF-a and our old friend NF-kB. This cocktail is also present in SASP and shows just how interconnected it all is.

My money is on Conboy being right and that this is a dilution of Pro-aging factors by young blood and hence they are working on a filter to calibrate aged blood like a dialysis machine.

Posted by: Steve Hill at September 15th, 2017 8:44 AM

Would regular blood donations help dilute the pro-aging factors?

Posted by: Corbin at September 15th, 2017 2:09 PM

I never quite understood the interest of this intensive focus on old blood plasma

Your body's cells are bathed in interstitial fluids with several times greater volume than blood, not to mention even several times more intracellular fluids, all full of "old bio-factors"

This old blood stuff is a true "drop in bucket"

Dilution will only be of transient nature no matter how you do it.

Posted by: Qui Jonglou at September 15th, 2017 3:07 PM

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